Interleukin (IL)-13 is a 114 amino acid cytokine with an unmodified molecular mass of approximately 12 kDa [McKenzie, A. N., et al. J Immunol, 1993.150 (12): p. 5436-44, and Minty, A., et al. Nature, 1993.362 (6417): p. 248-50.]. IL-13 is most closely related to IL-4 with which it shares 30% sequence similarity at the amino acid level. The human IL-13 gene is located on chromosome 5q31 adjacent to the IL-4 gene. This region of chromosome 5q contains gene sequences for other Th2 lymphocyte derived cytokines including GM-CSF and IL-5, whose levels together with IL-4 have been shown to correlate with disease severity in asthmatics and rodent models of allergic inflammation [Nakamura, Y., et al. Am J Respir Cell Mol Biol, 1996. 15 (5): p. 680-7, Robinson, D. S., et al. N Engl J Med, 1992.326 (5): p. 298-304, Walker, C., et al. Am J Respir Crit Care Med, 1994. 150 (4): p. 1038-48, Humbert, M., et al. Am J Respir Crit Care Med, 1996, 154 (5): p. 1497-504, Corrigan, C. J. and A. B. Kay Int Arch Allergy Appl Immunol, 1991. 94 (1-4): p. 270-1, Bentley, A. M., et al. Am J Respir Cell Mol Biol, 1993.].
Although initially identified as a Th2 CD4+ lymphocyte derived cytokine, IL-13 is also produced by Th1 CD4+ T-cells, CD8+ T lymphocytes NK cells, and non-T-cell populations such as mast cells, basophils, eosinophils, macrophages, monocytes and airway smooth muscle cells.
IL-13 is reported to mediate its effects through a receptor system that includes the IL-4 receptor a chain (IL-4Rα)-, which itself can bind IL-4 but not IL-13, and at least two other cell surface proteins, IL-13Rα1 and IL-13Rα2 [Murata, T., et al. Int J Hematol, 1999. 69(1): p. 13-20, Andrews, A. L., et al. J Biol Chem, 2002. 277(48): p. 46073-8.]. IL-13Rα1 can bind IL-13 with low affinity, subsequently recruiting IL-4Rα to form a high affinity functional receptor that signals [Miloux, B., et al. FEBS Lett, 1997.401 (2-3): p. 163-6, Hilton, D. J., et al. Proc Natl Acad Sci USA, 1996. 93 (1): p. 497-501]. The Genbank database lists the amino acid sequence and the nucleic acid sequence of IL-13Rα1 as NP 001551 and Y10659 respectively. Studies in STATE (signal transducer and activator of transcription 6)-deficient mice have revealed that IL-13, in a manner similar to IL-4, signals by utilizing the JAK-STAT6 pathway [Kuperman, D., et al. J Exp Med, 1998. 187 (6): p. 939-48, Nelms, K., et al. Annu Rev Immunol, 1999.17: p. 701-38.]. IL-13Rα2 shares 37% sequence identity with IL-13Rα1 at the amino acid level and binds IL-13 with high affinity [Zhang, J. G., et al. J Biol Chem, 1997.272 (14): p. 9474-80, Caput, D., et al. J Biol Chem, 1996.271 (28): p. 16921-6.]. However, IL-13Rα2 has a shorter cytoplasmic tail that lacks known signaling motifs. Cells expressing IL-13Rα2 are not responsive to IL-13 even in the presence of IL-4Rα[Kawakami, K., et al. Blood, 2001.97 (9): p. 2673-9]. It is postulated, therefore, that IL-13Rα2 acts as a decoy receptor regulating IL-13 but not IL-4 function. This is supported by studies in IL-13Rα2 deficient mice whose phenotype was consistent with increased responsiveness to IL-13 [Wood, N., et al. J Exp Med, 2003.197 (6): p. 703-709, Chiaramonte, M. G., et al. J Exp Med, 2003.197 (6): p. 687-701]. The Genbank database lists the amino acid sequence and the nucleic acid sequence of IL-13Rα2 as NP000631 and Y08768 respectively.